scholarly journals Integrated aqueous humor ceRNA and miRNA-TF-mRNA network analysis reveals potential molecular mechanisms governing primary open-angle glaucoma pathogenesis

2020 ◽  
Author(s):  
Xiaoqin Wang ◽  
Ming Chen ◽  
Liuzhi Zeng ◽  
Longqian Liu
Keyword(s):  
Gene Expression ◽  
Aqueous Humor ◽  
Molecular Mechanisms ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Gene Expression Omnibus ◽  
Open Angle ◽  
Pathway Enrichment ◽  
Protein Protein Interaction ◽  
Non Coding Rnas

AbstractPrimary open-angle glaucoma (POAG) is the leading cause of blindness globally, which develops through complex and poorly understood biological mechanisms. Herein, we conducted an integrated bioinformatics analysis of extant aqueous humor (AH) gene expression datasets in order to identify key genes and regulatory mechanisms governing POAG progression. We downloaded AH gene expression datasets (GSE101727 and GSE105269) corresponding to healthy controls and POAG patients from the Gene Expression Omnibus. We then identified mRNAs, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) that were differentially expressed (DE) between control and POAG patients. DEmRNAs and DElncRNAs were then subjected to pathway enrichment analyses, after which a protein-protein interaction (PPI) network was generated. This network was then expanded to establish lncRNA-miRNA-mRNA and miRNA-transcription factor(TF)-mRNA networks. In total, the GSE101727 dataset was used to identify 2746 DElncRNAs and 2208 DEmRNAs, while the GSE105269 dataset was used to identify 45 DEmiRNAs. We ultimately constructed a competing endogenous RNA (ceRNA) network incorporating 37, 5, and 14 of these lncRNAs, miRNAs and mRNAs, respectively. The proteins encoded by these 14 hub mRNAs were found to be significantly enriched for activities that may be linked to POAG pathogenesis. In addition, we generated a miRNA-TF-mRNA regulatory network containing 2 miRNAs (miR-135a-5p and miR-139-5p), 5 TFs (TGIF2, TBX5, HNF1A, TCF3, and FOS) and 5 mRNAs (SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2). The SHISA7, ST6GAC2, TXNIP, FOS, and DCBLD2 genes that may be viable therapeutic targets for the prevention or treatment of POAG, and regulated by the TFs (TGIF2, HNF1A, TCF3, and FOS).

scholarly journals Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma 

2020 ◽  
Author(s):  
Minwen Zhou ◽  
Bing Lu ◽  
Wei Tan ◽  
Mingshui Fu
Keyword(s):  
Gene Expression ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Functional Assay ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Regulate Gene Expression ◽  
Cerna Network

Abstract Background: Primary open angle glaucoma (POAG) is a multifactorial disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear. Methods: Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network. Results: During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched. Conclusion: This study provides novel insights into the lncRNA‑related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.

scholarly journals Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

2020 ◽  
Author(s):  
Minwen Zhou ◽  
Bing Lu ◽  
Wei Tan ◽  
Mingshui Fu
Keyword(s):  
Gene Expression ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Functional Assay ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Regulate Gene Expression ◽  
Cerna Network

Abstract Background Primary open angle glaucoma (POAG) is a complicated disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear. Methods Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network. Results During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched. Conclusion This study provides novel insights into the lncRNA-related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.

scholarly journals Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma 

2020 ◽  
Author(s):  
Minwen Zhou ◽  
Bing Lu ◽  
Wei Tan ◽  
Mingshui Fu
Keyword(s):  
Gene Expression ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Functional Assay ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Regulate Gene Expression ◽  
Cerna Network

Abstract Background: Primary open angle glaucoma (POAG) is a multifactorial disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear. Methods: Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network. Results: During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched. Conclusion: This study provides novel insights into the lncRNA‑related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.

scholarly journals Identification of lncRNA–miRNA–mRNA regulatory network associated with Primary Open Angle Glaucoma

2019 ◽  
Author(s):  
Minwen Zhou ◽  
Bing Lu ◽  
Wei Tan ◽  
Mingshui Fu
Keyword(s):  
Gene Expression ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Functional Assay ◽  
Retinal Ganglion ◽  
Open Angle ◽  
Regulate Gene Expression ◽  
Cerna Network

Abstract Background Primary open angle glaucoma (POAG) is a complicated disorder characterized by a progressive permanent degeneration of retinal ganglion cell (RGCs) death. An increasing number of studies have suggested that long noncoding RNAs (lncRNAs) have the ability to regulate gene expression; however, thus far, the mechanisms and functions of lncRNAs in the development of POAG are still unclear.Methods Using the data from Gene Expression Omnibus (GEO), differentially expressed lncRNAs and differentially expressed mRNAs between POAG patients and controls were identified. Then, the lncRNA–miRNA–mRNA competing endogenous RNA (ceRNA) network was constructed, and the key lncRNAs in POAG were identified. A Gene Ontology (GO) analysis and a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to assess the enriched biological functions of mRNA in the ceRNA network.Results During this study, a POAG-related ceRNA network with 37 miRNA nodes, 248 lncRNA nodes, 178 mRNA nodes, and 1985 edges was constructed. In addition, four lncRNAs (DNAJC27-AS1, AF121898, OIP5-AS1, and SNX29P2) were established as hub RNAs in this ceRNA network. The functional assay showed that 18 GO terms and 17 pathways were enriched.Conclusion This study provides novel insights into the lncRNA-related ceRNA network in POAG, and the four lncRNAs were identified in the development of POAG.

Detection of specific proteins in the aqueous humor in primary open-angle glaucoma

1990 ◽  
Vol 4 (1) ◽  
pp. 1 ◽  
Author(s):  
In Seop Lee ◽  
Young Suk Yu ◽  
Dong Myung Kim ◽  
Dong Ho Youn ◽  
Jin Q Kim
Keyword(s):  
Aqueous Humor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Open Angle ◽  
Specific Proteins

scholarly journals Profile of vascular and inflammatory aqueous humor cytokines in primary open angle glaucoma patients

2019 ◽  
Author(s):  
Ruyi Zhai ◽  
Huan Xu ◽  
Xinghuai Sun ◽  
Xiangmei Kong
Keyword(s):  
Aqueous Humor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Antibody Array ◽  
Open Angle ◽  
Aqueous Samples ◽  
Age Related ◽  
Tnf Α ◽  
Cytokine Antibody Array ◽  
Angiopoietin 2

Abstract Purpose: This study was aimed to analyze the profile of vascular and inflammatory cytokines in aqueous humor of primary open angle glaucoma (POAG) patients. Methods: Aqueous humor samples were acquired from 6 POAG patients and 7 age-related cataract patients that constituted the control group. A human cytokine antibody array was used to detect 37 proteins related to inflammation and vascular regulation. Characteristics including age, gender, and intraocular pressure (IOP) of POAG and age-related cataract patients were compared. Correlation analyses between aqueous humor cytokines and characteristics were performed. Results: The cytokine antibody array results showed that the signal intensities of soluble vascular endothelial growth factor receptor 1 (sVEGFR-1), von Willebrand factor (vWF), tumor necrosis factor (TNF)-α, and angiopoietin-2 in POAG patients were significantly higher in aqueous samples compared to controls (p < 0.05, Student’s test or Mann-Whitney U-test). Among cytokines of all aqueous samples, preoperative IOP was positively associated with expression quantity of sVEGFR-1 (r = 0.647, p = 0.02) and VEGF-A (r = 0.602, p = 0.04) and negatively associated with plasminogen activator inhibitor 1 expression (r = -0.593, p = 0.04). Values for sVEGFR-1 were positively correlated with vWF (r = 0.646, p = 0.02) and TNF-α (r = 0.824, p < 0.001) with statistical significance. Conclusion: Pathogenesis of primary open angle glaucoma may be associated with both vascular dysfunction and inflammatory responses. The vascular factors may include endothelial dysfunction and damaged vascular permeability as indicated by abnormal expression of vWF, sVEGFR-1 and angiopoietin-2. Keywords: POAG, aqueous humor, cytokines, sVEGFR-1, vWF, angiopoietin-2

scholarly journals Comparison of cytokine/chemokine levels in aqueous humor of primary open-angle glaucoma patients with positive or negative outcome following trabeculectomy

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Beata Gajda-Deryło ◽  
Thomas Stahnke ◽  
Stephan Struckmann ◽  
Gregor Warsow ◽  
Kerstin Birke ◽  
...  
Keyword(s):  
Growth Factor ◽  
Aqueous Humor ◽  
Transforming Growth Factor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Transforming Growth Factor Β ◽  
Positive Outcome ◽  
Open Angle ◽  
Antifibrotic Therapy ◽  
Cytokines And Chemokines

Abstract We aimed to identify differences in cytokine/chemokine levels in the aqueous humor (AH) of primary open-angle glaucoma (POAG) patients who suffered from scarring, compared with POAG patients with no scarring after trabeculectomy surgery. Identification of differently expressed cytokines and chemokines may help to understand scarring and fibrotic processes following trabeculectomy, and to make predictions for the outcome of fistulating surgery in the future. Furthermore, the identification of cell signaling pathways involved in fibrosis offers the opportunity for a more specific antifibrotic therapy with reduced side effects, and an improvement in long-term surgical outcome. Eight samples of AH were collected during trabeculectomy surgery and commercially available cytokine/chemokine arrays were used. Specific, differently expressed proteins (cytokines/chemokines) in AH samples from patients with positive and negative surgery outcomes were detected. These proteins were classified based on their known profibrotic, inflammatory, adhesive, and apoptotic properties. Transforming growth factor β (TGF-β) and vascular endothelial growth factor (VEGF) were among the most important profibrotic cytokines that we detected. Differences in the fold change of protein expression were highly significant between patients after successful and failed trabeculectomy surgery, and these were processed and visualized using ExprEssence software. This pilot study revealed differences in concentrations of cytokines/chemokines in AH between the two examined groups of patients. Our findings suggest that a positive outcome from trabeculectomy is strongly related to an inhibition of the fibrosis process.

Aqueous humor metabolite profile of pseudoexfoliation glaucoma is distinctive

2020 ◽  
Vol 16 (5) ◽  
pp. 425-435 ◽  
Author(s):  
Ciara Myer ◽  
Leila Abdelrahman ◽  
Santanu Banerjee ◽  
Ram B. Khattri ◽  
Matthew E. Merritt ◽  
...  
Keyword(s):  
Machine Learning ◽  
Aqueous Humor ◽  
Primary Open Angle Glaucoma ◽  
Open Angle Glaucoma ◽  
Metabolite Profile ◽  
Open Angle ◽  
Pseudoexfoliation Glaucoma

We identified 298 metabolites in pseudoexfoliation (PEX) glaucoma, primary open angle glaucoma (POAG) and non-glaucomatous controls. Machine learning can classify aqueous humor into the three distinct categories and presents the opportunity for future predictions.

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